Normal human thymus-derived lymphocytes (T-cells) may be stimulated to undergo blastic transformation in response to mitogenic stimulation. Early changes in the degree in nonhistone chromosomal protein phosphorylation have been documented to occur following this stimulation. Changes in the phosphorylation of the nonhistone chromosomal proteins have also been demonstrated to occur in association with alteration of chromatin structure and function in these cells stimulated to divide. Given the perturbations in the nonhistone proteins that occur upon stimulation of a quiescent cellular population to divide and given the differences in proliferative potential between normal and malignant lymphocytes, we propose to examine the nature of chromatin structural alterations that occur upon interaction with the phosphorylated nonhistone proteins derived from either normal or malignant T-cells in several phases of the cell cycle. The human malignant T-lymphocytes to be utilized will be cell lines CCRF-CEM and CCRF-HSB-2 derived from two children with lymphoblastic lymphoma. These human cell lines have been shown to be diploid or near diploid, form non-immune rosettes with sheep erythrocytes and lack any Epstein-Barr virus antigen, surface receptors for complement and surface immunoglobins. The chromatin structural alterations will be examined conformationally, utilizing circular dichroism and ethidium bromide intercalation, as well as in terms of helical stability determined by derivative thermal denaturation. The differential synthesis of phosphorylated nonhistone proteins and their differential binding to nucleohistone will also be examined in the cell populations under consideration.